Abstract
Several bis-amino acids were prepared using a bis-Suzuki coupling (compounds 4–8, 10), a sequential Michael addition and bis-Suzuki coupling (compounds 12, 13) and a Michael addition followed by a substitution reaction (compounds 18, 19). Thus, the pure stereoisomer of the methyl esters of N-(tert-butoxycarbonyl)-β-bromodehydroaminobutyric acid and dehydrophenylalanine and of N-benzyloxycarbonyl-β-bromodehydroaminobutyric acid were reacted with 1,4-phenylene-bis-boronic acid or 9,9-dioctyl-9H-fluorene-2,7-bis-boronic acid using modified Suzuki coupling conditions. The corresponding bis-dehydroamino acid derivatives were obtained in good to high yields maintaining the stereochemistry of the starting materials. This reaction was also applied successfully to a brominated dehydrodipeptide and 1,4-phenylene-bis-boronic acid showing that it could be used to create cross-links in peptide chains. An N,N-diacyldehydroalanine derivative was used in a sequential Michael addition and bis-Suzuki coupling giving a p-terphenyl bis-amino acid and a fluorenyl bis-amino acid in good yields. Two bis-α,β-diamino acids were obtained by a Michael addition of 1,2,4-triazole to the methyl esters of N-(4-toluenesulfonyl), N-(tert-butoxycarbonyl) dehydroamino acids followed by treatment with ethylenediamine.
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Acknowledgments
We acknowledge the Foundation for Science and Technology (FCT), Portugal and the Fundo Europeu de Desenvolvimento Regional (FEDER) for financial support through the Centro de Química of University of Minho and through the project POCI/QUI/59407/2004.
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Ferreira, P.M.T., Monteiro, L.S., Queiroz, MJ.R.P. et al. Synthesis of bis-amino acid derivatives by Suzuki cross-coupling, Michael addition and substitution reactions. Amino Acids 36, 429–436 (2009). https://doi.org/10.1007/s00726-008-0095-9
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DOI: https://doi.org/10.1007/s00726-008-0095-9